Disruption of thyroid hormone homeostasis at weaning of Holtzman rats by lactational but not in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Toxicol Sci. 2005 May;85(1):607-14. doi: 10.1093/toxsci/kfi122. Epub 2005 Feb 16.


The purpose of this study is to clarify whether lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is entirely responsible for the perturbation in thyroid hormone homeostasis during the neonatal period. Pregnant Holtzman rats were given a single oral dose of 1.0 mug TCDD/kg body weight on gestational day 15. Half of the litters were cross-fostered with the half of the dams treated with vehicle on postnatal day (PND) 1 to make four groups of rats, control (C/C), prenatal TCDD exposure only (T/C), postnatal TCDD exposure only (C/T), and both prenatal and postnatal TCDD exposure (T/T). On PND 21, the C/T and T/T groups, but not the T/C and C/C groups, showed a significant decrease in serum total thyroxin (TT4) and free thyroxin (FT4) concentrations in both sexes and a significant increase in serum thyroid-stimulating hormone (TSH) levels, particularly male pups. These two groups of male and female pups had significantly higher concentrations of TCDD in the liver, with marked induction of cytochrome P450 (CYP) 1A1 mRNA and intense immunostaining of CYP1A1 in the liver. UDP glycosyltransferase 1 family, polypeptide A6 (UGT1A6) and UGT1A7 mRNAs were induced in their livers, with marked immunostaining of UGT1A6. The transfer of TCDD from dams to the pups was confirmed by the detection of TCDD in mother's milk remaining in the stomachs of lactationally exposed pups on PND 1. The present results demonstrate that lactational, but not in utero, exposure to TCDD was responsible for the disruption of thyroid hormone homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Suckling
  • Cytochrome P-450 CYP1A1 / biosynthesis
  • Environmental Pollutants / pharmacokinetics
  • Environmental Pollutants / toxicity*
  • Female
  • Gestational Age
  • Homeostasis / drug effects*
  • Immunohistochemistry
  • Liver / drug effects
  • Liver / enzymology
  • Liver / growth & development
  • Liver / metabolism
  • Male
  • Milk / chemistry
  • Monosaccharide Transport Proteins / biosynthesis
  • Organ Size / drug effects
  • Polychlorinated Dibenzodioxins / pharmacokinetics
  • Polychlorinated Dibenzodioxins / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Hormones / metabolism*
  • Weaning


  • Environmental Pollutants
  • Monosaccharide Transport Proteins
  • Polychlorinated Dibenzodioxins
  • Thyroid Hormones
  • UDP-galactose translocator
  • Cytochrome P-450 CYP1A1